Autism. Autistic spectrum disorders (ASDs) are severe, chronic, pervasive disorders arising in early childhood. ASDs are characterized by deficits in all aspects of social interaction and reciprocity, pragmatic communication deficits and language delays, and an assortment of behavioral problems such as restricted interests, sensory sensitivities, and repetitive and stereotypic behaviors. The early onset of autism and its familial patterns of origin support a biological basis of origin. At the same time, evidence of a rapid increase in ASD incidence over the past several decades, the complex and highly varied genetic profiles of individuals with ASDs and the repeated demonstration that genetically-identical individuals may or may not develop ASD show that environmental factors also contribute importantly to the early neurological distortions that contribute to its onset.
The predominant scientific views of ASD origin focus on the severe deficits in “theory of mind” contributing to related impairments in “social cognition,” impairments in the development of normal language and related cognitive abilities, delayed and distorted development of executive and social control abilities, or on some form of more general “weak central coherence” impacting most or all brain systems at many or all brain processing levels.
Any theory on the cause of autism must account for the severe deficits in social cognition (SC) that are an invariable part of the disorder. The term “social cognition” refers to mental operations underlying social interactions including the: a) perception, processing and interpretation of information related to them, b) ability to perceive the intentions and dispositions of others; and c) generation and control of responses to those intentions. The scientific literature identifies at least five distinct SC domains: (1) emotion perception: the correct perception of facial and vocal expressions of the emotions in others; (2) social perception: the ability to judge social cues and infer social interactions from contextual information and nonverbal communicative gestures; (3) self-referential style: the explanations that people generate regarding the causes of positive and negative events in their lives (e.g., personalizing bias, “jumping to conclusions”, etc.); (4) theory of mind (ToM): the ability to attribute mental states to others, to make inferences about others' intentions, and to understand that others have mental states that differ from one's own, including false beliefs, hints, intentions, irony, sarcasm, etc.; and (5) empathy: the capability to share and understand other's emotions and feelings.
Recent studies in humans and primates have mapped brain areas related to these different dimensions of social cognition. For example, a distributed network of areas has been shown to be involved in the perception and interpretation of social information, with specific areas argued to sub-serve specific SC functions. The lateral fusiform gyrus, superior temporal sulcus and amygdala are activated by facial and emotion perception tasks. The medial frontal, medial prefrontal and orbitofrontal areas are engaged in ToM-related actions. The ventromedial prefrontal cortex is activated in tasks in which social knowledge guides behavior. The orbito-frontal cortex regulates the values that bias and shape self-referential style in social responding. And the anterior and middle cingulate cortex, the supplementary motor area and the anterior insula are engaged by empathic tasks.
Social cognition deficits characterize individuals with ASD. Impairments in SC associated with impairments in communication are signature deficits of ASD. A level of social functioning necessarily underlies personally and societally satisfactory social and general functionality. Signs of social dysfunction in ASD children are evident within the first 6-12 months of life, emerging earlier than do the hypersensitivities and the restricted and repetitive behaviors that are so strongly associated with ASD. These core deficits in social cognition are strong, persistent, cross-modal, and degrade all SC operations. They underlie the social difficulties that are so diagnostic of autistic spectrum disorders.
It should be noted that for children and adults with high-functioning autism (HFA) and Asperger Syndrome (AS), invariably-present social cognition impairments can be substantially or completely distinct from general cognitive abilities. For many of these individuals, “high functioning” in cognitive terms simply does not equate with “high functioning” in social terms. Because of this distinction in the penetration of different expressions of ASD, SC deficits have been argued to be more primal than ASD origins. This discrepancy between cognitive and social skills clearly affects the ability of adults with HFA and AS to secure employment and live independently, and contributes greatly to their predictably poorer quality of life—even while they may have an acceptable or even high level of cognitive ability and control.
Over the past decades, numerous studies have documented severe deficits of individuals with ASD in virtually every aspect of SC tested. ASD individuals have a poor ability to recognize or distinguish between facial emotions. They are impaired in understanding and interpreting prosodic elements of speech that convey emotion or social meaning. Children with ASDs do not appropriately pair gestures with vocalizations and facial expressions that mark different emotional states. Both adults and children are impaired in both their appreciation and their production of emotional expressions.
Children with ASD have severe problems with processing facial stimuli. They are less likely to attend to faces, are impaired in face discrimination, and have difficulty recognizing familiar faces. Opposite to normal individuals, ASD patients spend twice as much time looking at the mouth region than at the eyes, which convey more information about complex emotions.
Severe problems in social cue perception, empathy, affect regulation, self-monitoring and gaze perception have been documented in ASD individuals. Impairments in “theory of mind” (ToM) have been richly catalogued. Subjects with ASDs have particular difficulty judging emotions and mental states expressed by the faces, voices or gestures of others.
Abnormal brain areas subserving SC contribute to the origins and expressions of ASDs. According to one theory, an early developmental failure involving the amygdala has a cascading influence on the development of cortical areas that mediate social perception in the visual domain, specifically impacting the “face area” in the fusiform cortex in the ventral temporal lobe. Indeed, recent imaging studies have documented abnormal activation patterns in a distributed SC system in the brains of individuals with ASD that supports this general perspective. SC deficits are invariably paralleled by amygdala hypo-activation or dysfunction.
Correlational studies also link these patterns to the striking deficits in social perception and in early-stage processing abnormalities of facial expressions. Similarly, ASD deficits are expressed by abnormal functionality in the superior temporal sulcus and medial prefrontal cortex. Hypo-activation of the fusiform face area (FFA) has been recorded in several fMRI and PET investigations, along with abnormal structural changes in the right FFA in brains of males with ASD.
A general conclusion from this emerging body of literature is that the severe SC problems characterizing ASD individuals represent at least one of the most elemental expressions—and possibly the primary neurobehavioral problem—at the heart of these disorders.
Current interventions applied to remediate social cognition deficits in ASD have not proven to be satisfactorily effective. Several reports have documented limited positive outcomes achieved with group-based interventions. Clinicians have outlined suggestions and provided workbooks and guidelines for training HFAs and more severe ASD and PDD-NOS groups in SC. Despite relatively sparse and modest documentation of benefits, these methods have been widely applied in clinical and special education school environments. Some individualized therapies designed to improve social functioning have also been studied, again demonstrating positive but modest improvements in SC achieved through very extensive one-on-one therapy.
In general, approaches to SC training are idiosyncratic, fragmented, and grossly incomplete. Few interventions are based on any theoretical understanding of the neurological processes or systems that underlie SC deficits in ASD. For example, almost all treatment approaches rely exclusively on a top-down, direct instructional approach, with no targeting of core neuronal deficits underlying social impairments. Most interventions target one or a few aspects of SC. No strategy developed up to this time applies multi-faceted training to establish more effective social abilities at every SC system level. Moreover, while many interventions drive improvements on trained abilities, they have failed to result in any significant generalization to everyday situations. Group-based or individualized interventions also require trained, experienced personnel, impose geographical barriers for program delivery, and by their nature limit the number of individuals that can participate in or benefit from any given intervention.
ASDs and related Pervasive Developmental Disorders (PPDs) degrade the lives and prospects of about every 60th child brought into our world. Most affected individuals require a high level of ongoing support. Because of their hypersensitivities, their deficits in language and non-verbal expression and their often-severe limitations in social control, rehabilitation, education and home and school life can be very challenging for parents, therapists and teachers. Given their special demands, the support of these individuals is exceptionally costly. Special education services have to be achieved in small groups or one-on-one, and because many individuals have to be continually monitored into—and not infrequently through—adulthood. There is a pressing need for more effective treatment modalities.
Social Cognition. Apart from sufferers of ASD, a subpopulation of normal humans is socially undeveloped in ways that negatively impact their entire lives. For example, social cognition deficits are a near-universal aspect of normal aging, and are especially impactful in pathological aging. Special and more profound social cognition deficits also limit the lives and personal success of 1) other children and adults with a history of pervasive developmental disability; 2) patients with schizophrenia, where there is a severe degradation of social cognition and control; 3) patients with other psychiatric disorders including bipolar disorder, depression, obsessive-compulsive disorder, hoarding disorders, and anxiety disorders—among many others; and 4) individuals with a great variety of social conduct disorders including psychopathic disorders, and oppositional-defiant disorders—among many others.
The standard of care for social skills interventions includes group-based or individual therapies that are widely applied in clinical and special education school environments. Using an instructional approach, children are didactically taught—using educational, top-down instructional strategies dependent on executive function abilities—to practice social skills. But these abilities are commonly very impaired in socially impaired individuals.
While some of these practical and scientific approaches to SC training have shown good compliance and usually improve directly trained skills in the research environment, current available programs and interventions fall short. Indeed, most well-controlled studies of available SC training approaches have documented modest or no generalization to everyday social behaviors or control.
Positive improvements in social cognition are a crucial facet of establishing or restoring the health and life-quality of millions of children and adults with these (and other related social-impairment) conditions.
Schizophrenia.
Schizophrenia is a severe, chronic mental illness that affects more than two million individuals in the U.S. The healthcare burden attributable to schizophrenia is estimated at $62 billion annually, and is expected to grow as many treatment programs fail to successfully re-integrate these individuals into the larger society. These costs are largely incurred by the functional impairments in living, work, and everyday function, which are an essential diagnostic feature of the illness, found in many patients with schizophrenia. These poor functional outcomes are manifested by the high rates of unemployment, poor social and community functioning, reduced capabilities for independent living, and a generally reduced quality of life.
These fundamental deficits in functional ability in schizophrenia are largely attributable to pervasive and enduring impairments in social cognition (SC): the perception, interpretation and processing of social information. Individuals with schizophrenia exhibit deficits in all core domains of SC: emotion perception (the recognition of facial and vocal affect), social cue perception (the ability to detect and comprehend cues in a social context), theory of mind (the mental capacity to infer one's own and others' mental states), attributional style (attribution of causes of events to the self, to others, or to factors in the environment), and empathy (the ability to share, understand and appropriately react to the emotional states of others). Notably, impairments in each of these domains have been shown to have a significant impact on functional outcome in schizophrenia.
These fundamental, multi-domain SC impairments are not only directly linked with poor social functioning (i.e., inadequate social relationships, weak attachments, limited social support), but also underlie most critical factors of daily living in schizophrenia, such as occupational status, community functioning, independent living skills, relapse rate, and quality of life. Moreover, the degree of SC impairment is a stronger predictor of the level of everyday functional ability than are cognitive abilities or the severity of positive symptoms. This makes SC an important treatment target in schizophrenia. As the ultimate goal of therapeutic interventions is to improve life outcomes for patients, recovery of these individuals to the broader society is dependent upon the recovery of their SC abilities. The fact that SC deficits persist throughout the course of the illness, are seen in prodromal patients, and are even present in unaffected relatives of patients, further stresses their central role in schizophrenia and fuels the need for an effective, scalable treatment for SC deficits.
These severe and broad-ranging SC deficits in schizophrenia are rooted in anatomical and functional abnormalities within a complex brain network collectively termed “the social brain.” Specifically, significant anatomical and/or functional abnormalities have been localized to the superior temporal sulcus (STS), anterior insula, amygdala, medial prefrontal cortex (mPFC), and to the cingulate cortex, all are known to be critically involved in perception and processing of social information. Further, abnormally-weak connectivity between functionally-related, cortical and subcortical areas, as well as between sensory cortices and higher-level areas has led to a growing characterization of schizophrenia as an “information processing disorder”. Collectively, these abnormalities further imply that effective treatments for schizophrenia should target SC dysfunction from their neurological core, by aiming to improve the speed of processing and accuracy of stimulus representation of social information in the core brain areas which underlie SC.
Despite the importance of SC as a primary source of impairment, frustrating successful treatment and real-world recovery of patients with schizophrenia, there are currently no well-accepted or even broadly administered methods for improving SC function in this large patient group. Further, SC deficits are resistant to pharmacological treatments including second-generation antipsychotic medications that are effective for controlling positive symptom levels. Perhaps more surprisingly, new and demonstrably effective interventions for treating cognitive deficits in schizophrenia have been shown to have only limited impacts on social functioning—perhaps because SC deficits are associated with impaired function of neural networks that are largely distinct from, and parallel those subserving more general cognition. The delivery of an effective, practical, affordable, and scalable solution for this specific need is therefore of the highest clinical significance.
Several experimental, therapist-delivered approaches targeting social skills or SC have been developed over the last decade. These interventions are offered in relatively few clinics nationwide and are usually administered by trained professionals individually or in small groups over the course of several months. The therapist-administered options usually focus on emotion management and social skills building, and require multiple in-person visits to the clinic in the course of a few months. Recently, some computer-aided interventions have been created, but they are limited in scope (mainly target a single SC domain in isolation, facial affect recognition), have undergone only initial testing in schizophrenia, and are not used, to the best of our knowledge, in any clinical treatment programs.
While recent studies have shown the promise of social skills and SC interventions, to date, no single treatment has been widely adopted or is currently seeking FDA clearance for patient reimbursement, and there is no standard of care for SC treatment in schizophrenia. Although the various interventions differ from one another in dosage, mode of administration, and targeted deficit(s), the majority have the following traits in common. First, they use a ‘top-down’ training strategy, utilizing explicit instructions and coaching strategies in which participants are taught how to work around their deficits. These strategies rely heavily on executive control, declarative memory, and strategic thinking abilities, all of which are substantially impaired in schizophrenia, effectively limiting the potential benefits of this approach. Second, they employ limited stimulus variation, in which only a small number of social stimuli can be modeled in individual or group-administered sessions. Individuals are exposed to a limited set of socially relevant stimuli and scenarios, which may be reducing the potential for generalization beyond the context of therapy. Third, they use a a ‘one size fits all’ approach, whereby group interventions are administered in an identical format to all participants, without regard to individual differences in level of social functioning across the five major SC domains. Finally, they are not scalable or cost-effective, because they require highly-trained personnel and necessitate frequent visits to the clinic. The relatively large costs associated with their delivery therefore limit the scalability of these forms of treatment to the larger schizophrenia population.
Notably, the goal of SC interventions is to improve functional outcomes by improving social abilities. Rigorous studies that would elucidate the degree of recovery in SC function that must be achieved to support true real-world abilities are therefore highly required. Nonetheless, outcome studies involving the interventions described above have had important limitations, making it difficult to determine which therapeutic approach is actually most effective. First, sample sizes are often small, fail to rigorously account for heterogeneity in the schizophrenia population, and provide little basis for determining predispositions for training gains in the population. Second, the lack of adequate controls that are matched for intensity and experimenter contact have made it difficult to conclusively attribute performance gains to outcomes. Third, the use of only one or two, often non-standardized, SC or functional outcome measures limits our understanding to the true nature of intervention, and its potential for generalization outside the training setting.
In recent years, special emphasis has been given to the need for early intervention in schizophrenia. It is now acknowledged that the early phase of psychotic illness is crucial in terms of the emergence of a range of cognitive deficits that have prognostic implications, and that early intervention can potentially prevent further worsening of symptoms and improve functioning. An important target for early intervention is the domain of social cognition, the mental operations that underlie understanding, interpretation and perception of social information. Severe social cognition deficits, often comparable to those seen in chronic patients, have been repeatedly documented in early-phase schizophrenia. These deficits span the domains of affect perception, social cue perception, including gaze perception, theory of mind, and attributional style.
Importantly, social cognition deficits have been strongly associated with poor functional outcome in schizophrenia. Specifically, affect recognition and social perception have been each linked with community functioning, social problem solving and social skills. ToM, as well as affect perception and social perception, have been found to mediate the relationship between neurocognition and functional outcome. Surprisingly, however, only a few studies to date have examined the direct effects of social cognition training in young adult or early psychosis patients, and none have evaluated a computerized intervention. Studies testing the effects of Cognitive Enhancement Therapy, a computer-based cognitive training with group-based social skills training and of SCIT, a social cognitive group intervention in first episode patients report promising effects on neurocognitive, social cognitive and functional outcome measures. However, these encouraging outcomes are limited by the practicality of applying these treatments in many clinical settings, given long treatment durations, the need for a trained clinician team, and the necessity of organizing patient groups for program delivery.